Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts

结缔组织增生 癌症研究 转移 肝星状细胞 癌症 肿瘤进展 免疫系统 肿瘤发生 生物 胰腺癌 医学 肿瘤微环境 化学 免疫学 内科学 肿瘤细胞 内分泌学
作者
Sonakshi Bhattacharjee,Florian Hamberger,Aashreya Ravichandra,Max J. Miller,Ajay Nair,Silvia Affò,Aveline Filliol,LiKang Chin,Thomas Savage,Deqi Yin,Naita M. Wirsik,Adam Mehal,Nicholas Arpaia,Ekihiro Seki,Matthias Mack,Di Zhu,Peter A. Sims,Raghu Kalluri,Ben Z. Stanger,Kenneth P. Olive,Thomas Schmidt,Rebecca G. Wells,Ingmar Mederacke,Robert F. Schwabe
出处
期刊:Journal of Clinical Investigation [American Society for Clinical Investigation]
卷期号:131 (11) 被引量:236
标识
DOI:10.1172/jci146987
摘要

Cancer-associated fibroblasts (CAF) may exert tumor-promoting and tumor-suppressive functions, but the mechanisms underlying these opposing effects remain elusive. Here, we sought to understand these potentially opposing functions by interrogating functional relationships among CAF subtypes, their mediators, desmoplasia, and tumor growth in a wide range of tumor types metastasizing to the liver, the most common organ site for metastasis. Depletion of hepatic stellate cells (HSC), which represented the main source of CAF in mice and patients in our study, or depletion of all CAF decreased tumor growth and mortality in desmoplastic colorectal and pancreatic metastasis but not in nondesmoplastic metastatic tumors. Single-cell RNA-Seq in conjunction with CellPhoneDB ligand-receptor analysis, as well as studies in immune cell–depleted and HSC-selective knockout mice, uncovered direct CAF-tumor interactions as a tumor-promoting mechanism, mediated by myofibroblastic CAF–secreted (myCAF-secreted) hyaluronan and inflammatory CAF–secreted (iCAF-secreted) HGF. These effects were opposed by myCAF-expressed type I collagen, which suppressed tumor growth by mechanically restraining tumor spread, overriding its own stiffness-induced mechanosignals. In summary, mechanical restriction by type I collagen opposes the overall tumor-promoting effects of CAF, thus providing a mechanistic explanation for their dual functions in cancer. Therapeutic targeting of tumor-promoting CAF mediators while preserving type I collagen may convert CAF from tumor promoting to tumor restricting.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
现代小丸子完成签到 ,获得积分10
1秒前
缺水哥完成签到,获得积分10
1秒前
缺水哥发布了新的文献求助10
4秒前
1234发布了新的文献求助10
4秒前
1762120完成签到,获得积分10
4秒前
ZR关闭了ZR文献求助
6秒前
卖萌的秋田完成签到,获得积分10
6秒前
热情铭完成签到 ,获得积分10
7秒前
完美麦片完成签到,获得积分10
12秒前
lll完成签到,获得积分10
13秒前
务实鞅完成签到 ,获得积分10
14秒前
量子星尘发布了新的文献求助10
19秒前
mawenyu完成签到,获得积分10
20秒前
17完成签到,获得积分20
20秒前
高大的水壶完成签到,获得积分10
21秒前
英俊的铭应助wellyou采纳,获得10
23秒前
风中的向卉完成签到 ,获得积分10
26秒前
Mp4完成签到 ,获得积分10
26秒前
凌兰完成签到 ,获得积分10
26秒前
plain完成签到,获得积分10
27秒前
陌上花开完成签到,获得积分10
28秒前
29秒前
fg2477完成签到,获得积分10
30秒前
忙碌的数学人完成签到,获得积分10
30秒前
情怀应助Engen采纳,获得10
30秒前
HJJHJH完成签到,获得积分10
32秒前
Bob发布了新的文献求助10
33秒前
34秒前
35秒前
HJJHJH发布了新的文献求助50
36秒前
JW完成签到,获得积分10
36秒前
wanci应助张参采纳,获得10
37秒前
谦让的西装完成签到 ,获得积分10
38秒前
李演员完成签到,获得积分10
39秒前
fei菲飞完成签到,获得积分10
39秒前
41秒前
Zhaowx完成签到,获得积分10
41秒前
Theprisoners完成签到,获得积分0
41秒前
木子发布了新的文献求助30
41秒前
41秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038235
求助须知:如何正确求助?哪些是违规求助? 3575992
关于积分的说明 11374009
捐赠科研通 3305760
什么是DOI,文献DOI怎么找? 1819276
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022